PROJECT SUMMARY Mapp Biopharmaceutical, Inc. (Mapp) is developing antibody-based therapeutics to treat a number of infectious agents, including some of the most dangerous known to man: the filoviruses. Marburg virus is a filovirus endemic to Africa and causes an often lethal hemorrhagic fever. Presently there are no approved vaccines or therapeutics to treat Marburg virus infections and this remains a major unmet medical need. Along with its collaborators, Mapp has screened over 100 antibodies from a number of different species that bind to or neutralize Marburg virus in vitro. Several of these have been shown to block the infection of cells and a few have shown potency when tested in animal models of Marburg. Recently, several fully-human monoclonal antibodies have been identified and recovered from a Marburg virus infection survivor. MR191, the lead candidate and the focus of this proposal, has been shown to completely protect non-human primates when challenged with a lethal dose of Marburg virus or the related Ravn virus. Mapp proposes to develop MR191 as a therapeutic candidate to treat Marburg and Ravn virus infections. A Chinese Hamster Ovary (CHO) cell line to produce MR191 will be created, characterized, and cell banks will be generated. This cell line will support production of MR191 at a research scale that will be tested in a non-human primate model of Marburg virus infection to determine the therapeutic window (i.e., how late after infection can MR191 be administered and still result in 100% efficacy) as well as dose determination studies (i.e., what is the lowest dose that gives 100% efficacy). Additionally, the toxicity of MR191 will be evaluated in non-human primates and the data will enable the submission of a New Investigational Drug Application (IND) to the U.S. Food and Drug Administration. Upon completion of the scope of this project, Mapp will be positioned to produce MR191 in compliance with current Good Manufacturing Practices (cGMPs) in advance of submitting the IND. This will enable the conduct of the first-in-human studies for this important filovirus MCM.